The objective of this project, submitted in response to PA-10-009, Bioengineering Research Grants, is to understand how the continuous growth of the crystalline lens throughout the life span contributes to changes in the optical quality of the eye. The main hypotheses to be tested are: (1) Changes in the lens refractive index gradient due to the lens fiber cell compaction that occurs with lens growth are correlated with age-related changes in lens power and spherical aberration. (2) These changes account for the progressive loss of balance between corneal and internal ocular aberrations. The proposal has three specific Aims: Aim 1: To develop an age-dependent optical model of the crystalline lens with refractive index gradient New experimental methods will be developed to measure the refractive index gradient, refractive power and aberrations of the in vitro lens using optical coherence tomography. Once validated, these techniques will be used to quantify the optical parameters of the in vitro lens as a function of age. The data will be used to develop theoretical models and computational tools to model the changes in refractive index gradient due to lens growth and predict how these changes modify the power and aberrations of the crystalline lens. Aim 2: To quantify the contribution of the lens shape and refractive index gradient to ocular spherical aberration in vivo. The methods of Aim 1 will be extended to retrieve the in vivo lens index gradient, power, and spherical aberration from optical coherence tomography images of the anterior segment. The optical parameters of the in vivo human lens will be measured as a function of age to determine the role of lens growth on the spherical aberration of the lens and the balance between corneal and internal aberrations. Aim 3: To evaluate the contribution of the lens shape and refractive index gradient to the peripheral optics of the eye. We will apply our model by evaluating the contribution of the crystalline lens to the peripheral optical performance of the eye. The model lens will then be integrated into a whole eye model that will output the peripheral refraction and off-axis aberration in the relaxed and accommodated states, as a function of age. The data will be used to test the prediction that lens growth and accommodative changes produce changes in the peripheral refraction and off axis aberrations of the whole eye. The project will have a broad impact on the field of physiological optics at a fundamental level. Quantifying how lens power and aberrations change with age will help better understand refractive error and aberration development. By characterizing the contribution of lens growth to the ocular aberration state, the results will also help better predict the long-term outcome of aberration-guided vision correction procedures, and help design improved treatments that take into account age-changes in the lens to improve the long-term visual outcome. PUBLIC HEALTH RELEVANCE: The crystalline lens of the eye continuously grows throughout life. This growth is a factor in the development of refractive errors, such as myopia. It also produces changes in the optical quality of the lens which can negatively affect the long-term outcome of vision correction procedures. The goal of the project is to better understand how the continuous growth of the crystalline lens changes the optical quality of the eye. The project will help better understand refractive error development, help develop better treatments to prevent the development of refractive errors, and help design improved vision correction treatments.